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Research Update - Myelin Remodeling Through Experience Dependent Oligodendrogenesis

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Research Update - Myelin Remodeling Through Experience Dependent Oligodendrogenesis

Research Update - Myelin Remodeling  Through Experience Dependent Oligodendrogenesis
Jennifer Orthmann-Murphy

Myelin, a specialized structure formed by oligodendrocytes in the brain, wraps around the output portion of nerve projections called axons , providing insulation, protection and support for the axons so that they may send signals from one nerve to another throughout the brain and body. The goal of this research project was to determine whether life experience could change myelin. We used a cutting-edge technique called in vivo two-photon microscopy, which is an approach that allows for long-term monitoring of living cells — and their individual features — in the intact brain. 

We studied the cortex of the mouse brain, an area that contains more neurons than oligodendrocytes and myelin. In particular, we examined the area called the barrel cortex, which receives whisker sensory information. We found that new oligodendrocytes were born over the full course of an animal’s life, with half of the population of cells born after early adulthood. The oligodendrocyte precursor cells, which normally populate the adult brain and are a natural source of new oligodendrocytes, are able to make new oligodendrocytes well past “middle age” in a mouse. However, we also found that most of the precursor cells that attempt to change into oligodendrocytes do not survive. The new oligodendrocytes that are successfully formed in the cortex are highly stable, and their myelin sheaths rarely change once established. Interestingly, we found that, even in aging mice, there are long stretches of axon “cables” without myelin, indicating that intermittent myelination is an important feature of cortical neurons, but we do not yet know why these sparse bits of myelin are required by neurons.

Lastly, we tested how constant whisker stimulation might affect oligodendrocytes and myelin in the barrel cortex. We found that mice exposed to hanging beads for three weeks had a dramatic increase in the production of new oligodendrocytes, together forming hundreds of new myelin sheaths. This “sensory enrichment” experiment demonstrates that changes in life experience can alter how much myelin is present in neuronal circuits. Therefore, even in what may be considered a “mature” brain, myelination patterns are still flexible and subject to change. In addition, the low probability of new oligodendrocytes being successfully made by the precursor cells suggests that in order to develop effective remyelination therapies, we must better understand the mechanisms that stabilize these cells that are attempting to become mature oligodendrocytes.  Jennifer Orthmann-Murphy, M.D. Ph.D., is addressing the mechanisms of remyelination in her current research project. 

Jennifer Orthmann-Murphy, MD, PhD, prepared this summary of research that was published in Nature Neuroscience by Ethan G. HughesJennifer L. Orthmann-MurphyAbraham J. Langseth and Dwight E. Bergles. Dr. Hughes was a postdoctoral fellow in the Bergles laboratory, The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine and now has his own lab at the University of Colorado. Jennifer Orthmann-Murphy is also a postdoctoral fellow in the Bergles laboratory, as well as a clinical neuroimmunology fellow in the Department of Neurology, Johns Hopkins School of Medicine.